The LIR is currently studying prospectively one of the largest groups of patients with the vasculitic syndromes in the world. On the basis of clinical, pathophysiologic, immunopathogenic, and therapeutic results obtained over the last 19 years, we have designed a revised categorization scheme for the vasculitides which has now reached worldwide acceptance. On the basis of our observations, lymphomatoid granulomatosis is classified as a subset of malignant lymphoma and not as a primary vasculitis. We have described a new vasculitic syndrome termed the polyangiitis overlap syndrome. We have developed and instituted aggressive chemotherapeutic regimens consisting of chronically administered cyclophosphamide together with corticosteroids. This therapy has dramatically altered the 5-yr survival in patients with systemic vasculitis from 13% in untreated patients to 48% after treatment with corticosteroids to greater than 90% in our patients treated with both cyclophosphamide and corticosteroids. This therapeutic protocol was originally evaluated in our 140 patients with Wegener's granulomatosis but has been extrapolated and successfully used in treating other vasculitides such as polyarteritis nodosa, allergic angiitis and granulomatosis, isolated central nervous system vasculitis, Takayasu's arteritis, the acute vasculitis of Sjogren's syndromes, and the polyangiitis overlap syndrome. Our therapeutic protocols for the vasculitic syndromes are now used worldwide. We have observed certain unexpected longterm side effects of cyclophosphamide and are currently developing new therapeutic protocols for the vasculitic syndromes. In this regard, we have begun to treat patients who cannot tolerate or fail to respond to cyclophosphamide therapy with cyclosporin A. In addition, we have demonstrated the sensitivity of certain phases of the B cell cycle to corticosteroids, cyclophosphamide, and cyclosporin. These observations might explain the efficacy of these agents in certain diseases characterized by hyperreactivity of B cell function.